Ubiquitination of MHC Class II is required for development of regulatory but not conventional CD4(+) T cells

Liu, H; Wilson, KR; Schriek, P; Macri, C; Blum, AB; Francis, L; Heinlein, M; Nataraja, C; Harris, J; Jones, SA; Gray, DHD; Villadangos, JA; Mintern, JD

Author(s): Liu, H; Wilson, KR; Schriek, P; Macri, C; Blum, AB; Francis, L; Heinlein, M; Nataraja, C; Harris, J; Jones, SA; Gray, DHD; Villadangos, JA; Mintern, JD;
Details: Publication Year 2020-08-03,Volume 205,Issue #5,Page 1207-1216
Journal Title: J Immunol
Publication Type: Journal Article
Abstract: MHC class II (MHC II) displays peptides at the cell surface, a process critical for CD4(+) T cell development and priming. Ubiquitination is a mechanism that dictates surface MHC II with the attachment of a polyubiquitin chain to peptide-loaded MHC II, promoting its traffic away from the plasma membrane. In this study, we have examined how MHC II ubiquitination impacts the composition and function of both conventional CD4(+) T cell and regulatory T cell (Treg) compartments. Responses were examined in two models of altered MHC II ubiquitination: MHCIIKR(KI) (/KI) mice that express a mutant MHC II unable to be ubiquitinated or mice that lack membrane-associated RING-CH 8 (MARCH8), the E3 ubiquitin ligase responsible for MHC II ubiquitination specifically in thymic epithelial cells. Conventional CD4(+) T cell populations in thymus, blood, and spleen of MHCIIKR(KI/KI) and March8 (-/-) mice were largely unaltered. In MLRs, March8 (-/-), but not MHCIIKR(KI/KI), CD4(+) T cells had reduced reactivity to both self- and allogeneic MHC II. Thymic Treg were significantly reduced in MHCIIKR(KI/KI) mice, but not March8 (-/-) mice, whereas splenic Treg were unaffected. Neither scenario provoked autoimmunity, with no evidence of immunohistopathology and normal levels of autoantibody. In summary, MHC II ubiquitination in specific APC types does not have a major impact on the conventional CD4(+) T cell compartment but is important for Treg development.
Publisher: ASI
Research Division(s): Immunology
PubMed ID: 32747505
Publisher's Version: https://doi.org/10.4049/jimmunol.1901328
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2020-09-07 02:56:53

Last Modified: 2020-09-07 03:26:41